Camizestrant Plus Capivasertib Demonstrates Encouraging Activity in Endocrine-Resistant ER-Positive Breast Cancer

Clinical Summary:

• Design/Population: The SERENA-1 study evaluated camizestrant plus capivasertib in heavily pretreated patients with endocrine-resistant ER-positive, HER2-negative advanced breast cancer.
• Key Outcomes: Camizestrant plus capivasertib demonstrated encouraging antitumor activity, with an objective response rate of 37% and median progression-free survival of 8.3 months. The safety profile was consistent with the known profiles of the individual agents, with diarrhea and nausea among the most frequently reported adverse events.
• Clinical Relevance: These findings support combined selective estrogen receptor degradation and AKT inhibition as a potential treatment strategy for endocrine-resistant ER-positive, HER2-negative advanced breast cancer and warrant further evaluation in larger studies.

Results from the SERENA-1 trial demonstrated that camizestrant plus capivasertib produced encouraging antitumor activity with a manageable safety profile in heavily pretreated patients with endocrine-resistant ER-positive, HER2-negative advanced breast cancer.

“Endocrine therapy is designed to reduce ER signaling through direct or indirect mechanisms, and is a key component of the treatment of those with both early and advanced-stage HR-positive breast cancer,” stated Christos Vaklavas, MD, Huntsman Cancer Institute, Salt Lake City, Utah, and coauthors. “Many HR-positive breast cancers are controlled for some time by first-line [endocrine therapy] but subsequently become resistant, highlighting the need for novel [endocrine] and combination therapy approaches to address these mechanisms.” 

In this phase 1 dose-escalation and dose-expansion study, 29 premenopausal or postmenopausal patients with endocrine-resistant ER-positive, HER2-negative advanced breast cancer who were refractory or intolerant to prior therapy received 75 mg of once-daily camizestrant plus 400 mg of twice-daily capivasertib administered on a 4-days-on, 3-days-off schedule until disease progression or unacceptable toxicity. Primary efficacy end points included objective response rate (ORR), duration of response, clinical benefit rate, and progression-free survival (PFS). Safety was evaluated through adverse event monitoring.

At a median follow-up of 14.9 months, 6 patients remained on study treatment. The ORR was 37%, the 24-month clinical benefit rate was 51.7%, and median PFS was 8.3 months. Median treatment duration was 8.6 months for camizestrant and 7.3 months for capivasertib.

Grade ≥3 adverse events occurred in 48.3% of patients. The most common grade ≥3 events included diarrhea (10.3%), rash (6.9%), increased aspartate aminotransferase (6.9%), increased alanine aminotransferase (6.9%), and anemia (3.4%). Adverse events resulted in dose reductions of camizestrant in 27.6% of patients and capivasertib in 41.4% of patients. Four patients discontinued capivasertib because of adverse events, and no treatment-related deaths were reported.

“The combination showed encouraging evidence of significant clinical benefit and antitumor activity,” concluded Dr Vaklavas et al. “These results support further investigation of camizestrant 75 mg in combination with capivasertib 400 mg in patients with ER-positive, HER2-negative negative breast cancer.”

Source:

Vaklavas C, Oliveira M, Armstrong AC, et al. Camizestrant in combination with capivasertib for women with ER-positive, HER2-negative advanced breast cancer: results from SERENA-1. ESMO Open. Published online: January 26, 2026. doi:10.1016/j.esmoop.2025.106049